Differential trends in myocardial infarction mortality over 1975-2010 in France according to gender: An age-period-cohort analysis.

BACKGROUND: A dramatic reduction in mortality from myocardial infarction (MI) has been observed in France as in other western countries. The dynamics of this decline are likely to have differed according to age and sex. Our study sought to clarify the contributions of age, period and birth-cohort effects on post-MI mortality in France between 1975 and 2010 and to identify gender-specific trends. METHODS: Trends were analysed using an age-period-cohort (APC) model. MI mortality data were selected using the International Classification of Diseases (ICD) (8, 9 and 10th revision) codes from the French national mortality databases. RESULTS: Age-standardised MI mortality rates decreased by 70% from 1975 to 2010 in both sexes. Linear trend (drift) accounted for the majority of this decline and appeared very similar between genders. However, we found that increased MI mortality with advancing age was more pronounced in women than men beyond the age of 50. We also observed a slowdown in the decline among cohorts born after 1945, particularly in women. CONCLUSIONS: MI mortality showed a dramatic downward trend for the last 35years in France. The linear decline was modulated by cohort effects, whereas no major period effect was identified. This study also showed noticeable differential age and cohorts' effects between genders, especially the no longer decline in MI mortality for women born after World War II. This highlights the need for specific preventive measures to target this population in the future.

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study.

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.

Depression and mortality: artifact of measurement and analysis?

BACKGROUND: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data. METHODS: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. RESULTS: Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost. LIMITATIONS: Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied. CONCLUSIONS: These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.

Alcohol consumption patterns and body weight.

BACKGROUND/AIMS: The impact of alcohol on health depends on both the total amount ingested per week and the drinking pattern. Our goal was to assess the relationship between drinking occasions and anthropometric indicators of adiposity. METHODS: For this cross-sectional study, 7,855 men aged 50-59 years were recruited between 1991 and 1993 in France. Clinical and anthropometric data were obtained in a standardized clinical examination by trained staff. Alcohol intake was assessed by a questionnaire recording daily consumption of each type of alcohol during a typical week. RESULTS: 75% of the participants drank alcohol daily (264.7 ml per week). For a given total alcohol intake and after adjustment of confounders, the number of drinking episodes was inversely correlated with body mass index (p < 0.0001) and waist circumference (p < 0.0001). The odds ratio (95% confidence interval) for obesity was 1.8 (1.3-2.4) for occasional (1-2 days/week) and 1.6 (1.2-2.1) for frequent drinkers (3-5 days/week) compared with daily drinkers. This correlation was less pronounced in moderate (<140 ml/week) than intermediate consumers (140-280 ml/week). In heavy consumers (>280 ml/week), the intake was almost always daily. The results were similar for wine and beer consumption. CONCLUSION: Our findings suggest that drinking occasion is a risk indicator of obesity independent of total alcohol intake.

Do lifestyle behaviours explain socioeconomic differences in all-cause mortality, and fatal and non-fatal cardiovascular events? Evidence from middle aged men in France and Northern Ireland in the PRIME Study.

OBJECTIVE: To examine the contribution of lifestyle behaviours to the socioeconomic gradient in all-cause mortality, and fatal and non-fatal cardiovascular events. METHOD: 10,600 men aged 50-59 years examined in 1991-1994 in Northern Ireland (NI) and France and followed annually for deaths and cardiovascular events for 10 years. Baseline smoking habit, physical activity, and fruit, vegetable, and alcohol consumption were assessed. RESULTS: All lifestyle behaviours showed marked socioeconomic gradients for most indicators in NI and France, with the exception of percentage of alcohol consumers in NI and frequency of alcohol consumption in NI and France. At 10 years, there were 544 deaths from any cause and 440 fatal and non-fatal cardiovascular events. After adjustment for country and age, socioeconomic gradients were further adjusted for lifestyle behaviours. For total mortality, the median residual contribution of lifestyle behaviours was 28% and for cardiovascular incidence, 41%. When cardiovascular risk factors were considered in conjunction with lifestyle behaviours these percentages increased to 38% and 67% respectively. CONCLUSION: Lifestyle behaviours contribute to the gradient in mortality and cardiovascular incidence between socioeconomic groups, particularly for cardiovascular incidence, but a substantial proportion of these differentials was not explained by lifestyle behaviours and cardiovascular risk factors.

Contribution of lifetime smoking habit in France and Northern Ireland to country and socioeconomic differentials in mortality and cardiovascular incidence: the PRIME Study.

BACKGROUND: This study examines the contribution of lifetime smoking habit to the socioeconomic gradient in all-cause and smoking-related mortality and in cardiovascular incidence in two countries. METHODS: 10,600 men aged 50-59 years were examined in 1991-4 in centres in Northern Ireland and France and followed annually for 10 years. Deaths and cardiovascular events were documented. Current smoking habit, lifetime smoking (pack-years) and other health behaviours were evaluated at baseline. As socio-occupational coding schemes differ between the countries seven proxy socioeconomic indicators were used. RESULTS: Lifetime smoking habit showed marked associations with most socioeconomic indicators in both countries, but lifetime smoking was more than 10 pack-years greater overall in Northern Ireland and smoking patterns differed. Total mortality was 49% higher in Northern Ireland than in France, and smoking-related mortality and cardiovascular incidence were 93% and 92% higher, respectively. Both lifetime smoking and fibrinogen contributed independently to these differentials, but together explained only 42% of the difference in total mortality between countries, adjusted for both biological and lifestyle confounders. Socioeconomic gradients were steeper for total and smoking-related mortality than for cardiovascular incidence. Residual contributions of lifetime smoking habit ranged from 6% to 34% for the seven proxy indicators of socioeconomic position for total and smoking-related mortality. Socioeconomic gradients in cardiovascular incidence were minimal following adjustment for confounders. CONCLUSION: In Northern Ireland and France lifetime smoking appeared to explain a significant part of the gradients in total and smoking-related mortality between socioeconomic groups, but the contribution of smoking was generally small for cardiovascular incidence.

Systemic chemokine levels, coronary heart disease, and ischemic stroke events: the PRIME study.

OBJECTIVES: To quantify the association between systemic levels of the chemokine regulated on activation normal T-cell expressed and secreted (RANTES/CCL5), interferon-γ-inducible protein-10 (IP-10/CXCL10), monocyte chemoattractant protein-1 (MCP-1/CCL2), and eotaxin-1 (CCL11) with future coronary heart disease (CHD) and ischemic stroke events and to assess their usefulness for CHD and ischemic stroke risk prediction in the PRIME Study. METHODS: After 10 years of follow-up of 9,771 men, 2 nested case-control studies were built including 621 first CHD events and 1,242 matched controls and 95 first ischemic stroke events and 190 matched controls. Standardized hazard ratios (HRs) for each log-transformed chemokine were estimated by conditional logistic regression. RESULTS: None of the 4 chemokines were independent predictors of CHD, either with respect to stable angina or to acute coronary syndrome. Conversely, RANTES (HR = 1.70; 95% confidence interval [CI] 1.05-2.74), IP-10 (HR = 1.53; 95% CI 1.06-2.20), and eotaxin-1 (HR = 1.59; 95% CI 1.02-2.46), but not MCP-1 (HR = 0.99; 95% CI 0.68-1.46), were associated with ischemic stroke independently of traditional cardiovascular risk factors, hs-CRP, and fibrinogen. When the first 3 chemokines were included in the same multivariate model, RANTES and IP-10 remained predictive of ischemic stroke. Their addition to a traditional risk factor model predicting ischemic stroke substantially improved the C-statistic from 0.6756 to 0.7425 (p = 0.004). CONCLUSIONS: In asymptomatic men, higher systemic levels of RANTES and IP-10 are independent predictors of ischemic stroke but not of CHD events. RANTES and IP-10 may improve the accuracy of ischemic stroke risk prediction over traditional risk factors.

Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: the PRIME study.

OBJECTIVE: Insulin-like growth factor-1 (IGF-1) has been associated with cardiovascular risk factors and atherosclerosis. The aim of the present study was to evaluate the prognostic value of IGF-1 concentrations with respect to occurrence of well-defined coronary syndromes. METHODS: The PRIME study is a prospective cohort having included 10,600 subjects from Northern Ireland and France. Detailed information on cardiovascular risk factors, socioeconomic and behavioural variables were collected and a cardiologic examination was performed. At 5-year follow-up, 317 incident cases of coronary events were recorded according to strict protocols. They were matched to 634 age- and centre-paired controls from the same cohort, free of coronary disease. Baseline IGF-1 concentrations were measured, together with variables of lipid and glucose metabolism and markers of vascular and systemic inflammation. RESULTS: Baseline IGF-1 concentration was lower in subjects developing an acute coronary syndrome than in unaffected controls. IGF-1 levels correlated negatively with age, waist circumference, tobacco consumption and markers of inflammation. Subjects in the highest quartile of IGF-1 distribution had a 55% reduction in the relative risk of developing myocardial infarction and a 45% decrease for all-combined acute coronary syndromes. A similar trend, although non-significant, was noted for angina pectoris. Multiple adjustments on classical risk factors and inflammation markers did not affect IGF-1 results. Elevated levels of both IGF-1 and apo A-I conferred a significantly greater risk reduction than either one alone. However, interaction between the two markers was not significant. CONCLUSION: Like HDL markers, high levels of IGF-1 confer protection against coronary artery disease.

Resting heart rate, mortality and future coronary heart disease in the elderly: the 3C Study.

OBJECTIVES: To investigate the association between resting heart rate (RHR) and mortality and incident coronary heart disease (CHD) in the elderly. METHODS: Data derived from the Three-City Study, a French multicentre prospective study including 9294 community-dwelling elderly subjects aged ≥65 years at baseline examination between 1999 and 2001. The study population comprised 7147 participants (61% women) who were free of a pacemaker or any cardiac arrhythmias at baseline. RHR was measured twice at baseline in a seated position using an electronic tensiometer. Participants were then followed up bi-annually for vascular morbidity and mortality over 6 years. CHD events and cardiovascular death were adjudicated by an independent expert committee. RESULTS: After 6 years of follow-up, 615 subjects died including 17.9% from cardiovascular causes. Subjects from the top quintile of RHR (>79 bpm) had respectively a 74% (95% CI, 1.3-2.3), a 87% (95% CI: 0.98-3.6, p = 0.06) and a 72% (95% CI, 1.3-2.3) increased risk of total, cardiovascular and non-cardiovascular mortality compared to those from the lowest quintile (<62 bpm), after adjustment for cardiovascular risk factors and beta-blocker (BB) use in a Cox regression analysis. Associations with total mortality were consistent according to age, gender, BB use, diabetes and hypertension status (all p values for interaction >0.10). Conversely, RHR was not predictive of incident CHD (n = 228 events; top vs lowest quintile: HR: 1.0; 95% CI: 0.6-1.5). CONCLUSIONS: RHR is an independent risk marker of mortality but not of incident CHD events in community-dwelling elderly. Its routine measurement may help identify those who are at increased risk of mortality in the short term.

Predicting CHD risk in France: a pooled analysis of the D.E.S.I.R., Three City, PRIME, and SU.VI.MAX studies.

BACKGROUND: We aimed to develop and validate a simple coronary heart disease (CHD) risk algorithm applicable to asymptomatic men and women in France, and to compare its accuracy with that of the last published version of the Framingham risk function for cardiovascular disease. DESIGN: A pooled analysis of four French prospective general-population studies. METHODS: The baseline and follow-up data from D.E.S.I.R., PRIME, Three City, and SU.VI.MAX studies were used. The 10-year CHD risk was estimated by the Cox proportional hazards model with candidate variables including age, gender, body mass index, waist circumference, family history of coronary heart disease, smoking status, diabetes status, systolic blood pressure, and total and high-density lipoprotein (HDL) cholesterol. RESULTS: The study population included 22,256 subjects (61.4% men) aged (SD) 56.0 years (8.3) without a personal history of CHD at baseline. After a mean follow-up of 8.0 years (2.3), 788 first CHD events occurred, 726 in men and 62 in women. The final model included age, gender, age × gender interaction, current smoking status, diabetes status, systolic blood pressure, total and HDL cholesterol. Using this model, the number of predicted coronary events fitted that given by the 10-year Kaplan-Meier survival estimates within each decile of estimated risk (calibration). This model had fair discrimination: Harrell C-index, 0.7831 (95% CI: 0.7704-0.7957). For comparison, the recalibrated Framingham risk function had equivalent performances compared to the French risk equation. CONCLUSION: Our 10-year French CHD risk equation based on traditional risk factors performed at least as well as the recalibrated Framingham cardiovascular disease risk function.

Do lipids and apolipoproteins predict coronary heart disease under statin and fibrate therapy in the primary prevention setting in community-dwelling elderly subjects? The 3C Study.

PURPOSE: To evaluate associations of standard lipids and apolipoproteins with incident coronary heart disease (CHD) in older adults according to lipid-lowering treatment (LLT) in the primary prevention setting. METHODS: Within the 3C Study of men and women aged ≥ 65 years, standard lipids, apolipoproteins A-1 and B100 and hs-CRP were measured in baseline blood samples from 199 participants who developed a first CHD event over 4 years of follow-up and from 1081 subjects randomly selected from the initial cohort (case cohort study). Standardized hazard ratios (HRs) were estimated by the Cox proportional hazard model. RESULTS: In the random sample, 75.3% were free of LLT (non-users), 11.5% received statins and 13.4% fibrates. Among the non-users, all lipid parameters were significantly associated with future CHD (n = 145) after adjustment for age, gender, study center and educational level, and their HRs were comparable. For instance, the HR for LDL-cholesterol was 1.38 (95% CI: 1.13-1.69). These associations also existed and were stronger among statin users (n = 27 CHD), as shown by an HR for LDL-cholesterol of 2.20 (95% CI: 1.27-3.81). Additional adjustment for traditional risk factors and hs-CRP marginally modified HR estimates in those receiving or not receiving statins. Among fibrate users (n = 27 CHD), significant associations were observed for triglycerides only (1.68; 95% CI = 1.04-2.72) in fully adjusted analyses. CONCLUSION: In older adults, standard lipids and apolipoproteins are stronger predictors of CHD in those receiving statins than in those who are not in the primary prevention setting. Under fibrate treatment, only triglycerides were independent predictors of CHD.

Association between the frequency of fruit and vegetable consumption and cardiovascular disease in male smokers and non-smokers.

BACKGROUND/OBJECTIVES: Consumption of fruit and vegetables (F&V) is associated with a lower cardiovascular disease (CVD) risk. Smoking may affect the strength of this association. The objective of this study was to compare the relationship between the frequency of F&V intake and CVD risk in male current, former and never smokers. SUBJECTS/METHODS: A prospective study in men (n=8060) aged 50-59 years who were recruited in France and Northern Ireland. The frequency of F&V intake was assessed by using a food frequency questionnaire. The outcome criteria were incident cases of acute coronary syndrome (ACS) and total CVD (coronary heart disease and stroke) over 10-year period. RESULTS: A total of 367 ACS and 612 CVD events occurred during the follow-up period. A multivariate analysis revealed a statistically significant interaction between smoking status and F&V intake for ACS and for CVD (both P's<0.05). In current smokers, the relative risks for ACS were 0.78 (0.54-1.13) and 0.49 (0.30-0.81) in the second and third tertiles of F&V intake, respectively (P for trend<0.001); for CVD, the values were 0.80 (0.59-1.08) and 0.64 (0.44-0.93) respectively (P for trend<0.001). In contrast, no statistically significant associations were observed for never and former smokers. Similar statistical interactions for ACS were observed for fruit intake (P=0.07) and vegetable intake (P<0.05) taken separately. CONCLUSIONS: These results suggest that high fruit and vegetable intake is associated with a lower risk of CVD in male smokers.

Waist circumference and obesity-related abnormalities in French and Cameroonian adults: the role of urbanization and ethnicity.

OBJECTIVES: To evaluate the effect of urbanization and ethnicity on correlations between waist circumference (WC) and obesity-related cardiovascular risk factors. METHODS: 1471 rural and urban Cameroonians, and 4185 French, from community-based studies, aged > or =25 years, not treated for hypertension, diabetes and dyslipidemia participated in this study. Slopes of obesity-related abnormalities with WC were compared using an interaction term between place of residence and WC. RESULTS: Women in urban Cameroon and men in France had significantly higher WC and BMI relative to their gender counterparts. Urban Cameroonians had higher abdominal adiposity, but lower BP and better metabolic profile than the French. WC was positively associated to all the obesity-related abnormalities in the three sites except to FPG (both genders) and blood lipids (women) in rural Cameroon. A 5 cm larger WC was associated with a higher increment among urban than rural Cameroonians for diastolic blood pressure (DBP) (women, 1.95/0.63 mm Hg; men, 2.56/1.44 mm Hg), HOMA-IR (women, 0.11/0.05), fasting plasma glucose (FPG) (men, 0.09/-0.01 mmol/l) and triglycerides (women, 0.06/0.01 mmol/l; men, 0.09/0.03 mmol/l), all P<0.05. A 5 cm larger WC was associated with a higher increment among urban Cameroon than French people for DBP (women, 1.95/1.28 mm Hg, P<0.01; men, 2.56/1.49 mm Hg, P<0.01), but with a lower increment for HOMA-IR (women, 0.11/0.14, P<0.05), FPG (women, 0.05/0.09 mmol/l), total cholesterol (women, 0.07/0.11 mmol/l; men, 0.10/0.13 mmol/l) and triglycerides (women, 0.06/0.11 mmol/l; men, 0.09/0.13 mmol/l) all P<0.05. CONCLUSION: Ethnicity and urbanization modify the association of WC with obesity-related metabolic abnormalities. WC cutoff points derived from Caucasians may not be appropriate for black Sub-Saharan Africans.

Adipocytokines and the risk of coronary heart disease in healthy middle aged men: the PRIME Study.

BACKGROUND: Adipokines play an important role in glucose, lipid and lipoprotein metabolisms, as well as in coagulation and inflammatory processes. So far, studies have evaluated the association of individual adipokines with future coronary heart disease (CHD) event and provided mixed results. OBJECTIVES: We sought to investigate the association of a set of adipocytokines, including total adiponectin, adipsin, resistin, leptin and plasminogen activator inihibitor-1 (PAI-1), with future CHD events in apparently healthy men. METHODS: We built a nested case-control study within the PRIME Study, a multicenter prospective cohort of 9779 healthy European middle-aged men. Total adiponectin, adipsin, resistin, leptin and PAI-1 were measured in the baseline plasma sample of 617 men who developed a first CHD event (coronary death, myocardial infarction, stable or unstable angina) during 10 years of follow-up and in 1215 study-matched controls, by multiplex assays using commercial kits. HRs for CHD were estimated by conditional logistic regression analysis. RESULTS: Median concentrations of total adiponectin, adipsin and resistin were similar in cases and in controls, whereas those of leptin and PAI-1 were higher in cases than in controls, 6.30 vs 5.40 ng ml(-1), and 10.09 vs 8.48 IU ml(-1), respectively. The risk of future CHD event increased with increasing quintiles of baseline leptin and PAI-1 concentrations only in unadjusted analysis (P-value for trend <0.003 and <0.0001, respectively). However, these associations were no longer significant after adjustment for usual CHD risk factors including hypertension, diabetes, smoking, total cholesterol, triglycerides and HDL cholesterol. Conversely, baseline CRP and IL-6 levels remained associated with CHD risk in multivariate analysis. CONCLUSIONS: In apparently healthy men, circulating total adiponectin, adipsin, resistin, leptin and PAI-1 were not independent predictors of future CHD event.

Anthropometric assessment of abdominal obesity and coronary heart disease risk in men: the PRIME study.

OBJECTIVE: Waist-to-height ratio is an anthropometric indicator of abdominal obesity that accounts for stature. Earlier studies have reported marked associations between the waist-to-height ratio and cardiovascular risk factors. The goal of this study was to compare the associations of waist-to-height ratio, waist girth, waist-to-hip ratio or body mass index (BMI) with incidence of coronary events. DESIGN: Prospective study with 10 602 men, aged 50-59 years, recruited between 1991 and 1993 in three centres in France and one centre in Northern Ireland. Clinical and biological data were obtained at interview by trained staff. During the 10 years of follow-up 659 incident coronary events (CHD) were recorded. The relations between anthropometric markers and coronary events were estimated by Cox proportional hazards models. RESULTS: Waist circumference, waist-to-hip ratio, waist-to-height ratios and BMI were positively associated with blood pressure (p<0.0001), diabetes (p<0.0001), low-density lipoprotein (LDL)-cholesterol (p<0.0001), triglycerides (p<0.0001) and inversely correlated to high-density lipoprotein (HDL)-cholesterol (p<0.0001). There was a linear association between waist circumference, waist-to-hip ratio, waist-to-height ratio, BMI and CHD events. The age-adjusted and centre-adjusted relative risks (95% CI) for CHD were 1.57 (1.22 to 2.01), 1.75 (1.34 to 2.87), 2.3 (1.79 to 2.99) and 1.99 (1.54 to 2.56) in the 5th quintile vs the first quintile of waist circumference, waist-to-hip ratio, waist-to-height ratio and BMI distribution, respectively. After further adjustment for school duration, physical activity, tobacco and alcohol consumption, hypertension, diabetes, HDL-cholesterol and triglycerides, the relative risks for CHD were 0.99 (0.76 to 1.30) for waist circumference (p = 0.5), 1.22 (0.93 to 1.60) for waist-to-hip ratio (p = 0.1), 1.53 (1.16 to 2.01) for waist-to-height ratio (p = 0.03) and 1.30 (0.99 to 1.71) for BMI (p = 0.06). CONCLUSION: In middle-aged European men, waist-to-height ratio identifies coronary risk more strongly than waist circumference, waist-to-hip ratio or BMI, though the difference is marginal.

Menopause and modifiable coronary heart disease risk factors: a population based study.

OBJECTIVES: The aim of our study was to determine the effect of the menopause on various coronary heart disease (CHD) risk factors and on the global risk of CHD in a population based sample of women, making the difference between menopause and age related effects. STUDY DESIGN: The Third French MONICA cross-sectional survey on cardiovascular risk included 1730 randomly selected women, aged 35-64 years, representative from the general population. MAIN OUTCOME MEASURES: Women were defined as post-menopausal (postM; n=696), peri-menopausal (periM; n=183) or pre-menopausal (preM; n=659) based on the date of last menses. Socio-demographic, clinical and biological data were collected. Analyses of variance were used to compare means. RESULTS: PostM women had significantly higher age-adjusted levels of total cholesterol (6.0mmol/L in postM vs. 5.7mmol/L in preM, p<0.05) and LDL cholesterol (3.9mmol/L vs. 3.6mmol/L, p<0.05). There was no difference in HDL cholesterol or triglyceride levels, glycemia or blood pressure. Further adjustment on body mass index and hormonal treatments did not modify the results. No risk factor was significantly different between periM and postM. However, the Framingham 10-year risk of CHD was higher in postM, as compared with periM (5.1% vs. 5.0%, p<0.05). In postM women, lipids and the Framingham risk were not associated with elapsed time since menopause. CONCLUSIONS: The CHD risk increases during the sixth decade could be explained not only by estrogen deprivation but also by an effect on lipid profile, which is likely to occur in the peri-menopause period.

Residual cardiovascular risk in treated hypertension and hyperlipidaemia: the PRIME Study.

Although pharmacological treatments of hypertension and dyslipidaemia are both associated with a reduction in cardiovascular risk, little is known about the degree of cardiovascular risk remaining in treated individuals, by assessing the levels of their risk factors achieved, that is their 'residual cardiovascular risk'. We then used the data from the Prospective Epidemiological Study of Myocardial Infarction (PRIME), which involved 9649 men aged 50-59 years, from France and Northern Ireland with a 10-year follow-up, to test the presence of specific residual cardiovascular risks of coronary heart disease, stroke, total of fatal and non-fatal cardiovascular events and cardiovascular mortality, in patients treated with antihypertensive agents or lipid-lowering agents. In the whole cohort, a total of 796 patients developed a fatal or non-fatal cardiovascular event. Antihypertensive drug use at baseline was significantly associated (RR=1.50, 95% CI: 1.25-1.80) with total cardiovascular event risk, but not lipid-lowering drug use, after adjusting for classic risk factors (age, smoking, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure and diabetes). Similar results were obtained for coronary heart disease (RR=1.46, 95% CI: 1.18-1.80), stroke (RR=1.75, 95% CI: 1.14-2.70) and cardiovascular death (RR=1.62, 95% CI: 1.02-2.58), but neither for total death (RR=1.15, 95% CI: 0.89-1.48) nor for non-cardiovascular death (RR=1.00, 95% CI: 0.74-1.36). For any cardiovascular end point, residual risks did not globally differ according to the antihypertensive drug class prescribed at baseline. In conclusion, treatment with antihypertensive agents, but not with lipid-lowering agents, was associated with a sizeable residual cardiovascular risk, suggesting that more efficient risk reduction strategies in hypertension should be developed as a priority.

Elevated plasma fibrin D-dimer as a risk factor for vascular dementia: the Three-City cohort study.

BACKGROUND: Hemostatic biomarkers have been associated with coronary heart disease (CHD) and stroke. However, few studies have investigated these associations in the elderly. Moreover, vascular factors may be involved in dementia. Data on the relationship between hemostatic biomarkers and dementia remain scarce. OBJECTIVES: Our study aimed to investigate the relationship between hemostatic biomarkers and the risk of CHD, stroke and dementia in an elderly population. PATIENTS/METHODS: In the Three-City cohort study including men and women aged > or = 65, we investigated the association of fibrinogen, D-dimer and von Willebrand factor with the 4-year incidence of arterial disease (CHD, n = 199; and stroke, n = 111) and dementia (n = 218). Measurements were performed for all cases and for a random sample of the entire cohort (n = 1254). Hazards ratios (HR) compared the last quintile with the first of each parameter's distribution and P-values refer to the test for linear trend across quintiles. RESULTS: Elevated fibrinogen was associated with the risk of CHD and myocardial infarction (HR = 2.20, P < 0.05 and 2.45 P < 0.05, respectively). Moreover, high D-dimer was associated with the risk of CHD among younger subjects (aged < 75, HR = 3.64, P < 0.01) but not older subjects (P for interaction = 0.01). Furthermore, the risk of vascular dementia (VaD) increased with D-dimer level (HR = 3.05, P < 0.01). CONCLUSIONS: In the elderly, elevated fibrinogen and D-dimer levels were associated with incident arterial disease. In addition, high D-dimer level could represent a new risk factor for VaD.

Association between angiopoietin-like 6 (ANGPTL6) gene polymorphisms and metabolic syndrome-related phenotypes in the French MONICA Study.

AIM: Although the ANGPTL6 (angiopoietin-like 6) gene product is now known to be involved in the regulation of fat mass and insulin sensitivity in mice, its physiological functions in humans have yet to be determined. METHODS: Subjects from the population-based French MONICA Study (n=3402) were genotyped for single nucleotide polymorphisms (SNPs) in ANGPTL6, and associations with anthropometric or biochemical phenotypes were looked for. RESULTS: On evaluating the frequency of 17 ANGPTL6 SNPs in 100 randomly selected subjects on the basis of linkage disequilibrium mapping, four SNPs (rs6511435, rs8112063, rs11671983 and rs15723) were found to cover more than 95% of the known ANGPTL6 genetic variability. Subjects from the entire MONICA Study were then genotyped for these four SNPs. No significant association was detected for rs11671983 and rs15723. In contrast, the G allele of rs8112063 was associated with lower plasma glucose levels (P=0.009). Also, obese subjects carrying the G allele of rs6511435 had higher plasma insulin levels than AA subjects (P=0.0055). Moreover, the G allele of rs6511435 tended to be associated with a 20% higher risk of the metabolic syndrome (P=0.034). However, when false discovery rate testing (40 tests) was applied, these associations were no longer statistically significant. CONCLUSION: These findings constitute the first study in humans of ANGPTL6 genetic variability. Although there was no evidence that polymorphisms in ANGPTL6 might be significantly associated with the metabolic syndrome-related phenotypes, a weak association of these polymorphisms with these parameters cannot be excluded. Further association studies are needed to arrive at any definite conclusions.

Association of macronutrient intake patterns with being overweight in a population-based random sample of men in France.

AIM: Diet is considered an important modifiable factor in the overweight. The role of macronutrients in obesity has been examined in general in selected populations, but the results of these studies are mixed, depending on the potential confounders and adjustments for other macronutrients. For this reason, we examined the association between macronutrient intake patterns and being overweight in a population-based representative sample of middle-aged (55.1+/-6.1 years) men (n=966), using various adjustment modalities. METHODS: The study subjects kept 3-day food-intake records, and the standard cardiovascular risk factors were assessed. Weight, height and waist circumference (WC) were also measured. RESULTS: Carbohydrate intake was negatively associated and fat intake was positively associated with body mass index (BMI) and WC in regression models adjusted for energy intake and other factors, including age, smoking and physical activity. However, with mutual adjustments for other energy-yielding nutrients, the negative association of carbohydrate intake with WC remained significant, whereas the associations between fat intake and measures of obesity did not. Adjusted odds ratios (95% confidence interval) comparing the highest and lowest quartiles of carbohydrate intake were 0.50 (0.25-0.97) for obesity (BMI>29.9) and 0.41 (0.23-0.73) for abdominal obesity (WC>101.9 cm). CONCLUSION: Consistent negative associations between carbohydrate intake and BMI and WC were seen in this random representative sample of the general male population. The associations between fat intake and these measures of being overweight were attenuated on adjusting for carbohydrate intake. Thus, the balance of carbohydrate-to-fat intake is an important element in obesity in a general male population, and should be highlighted in dietary guidelines.